Central sleep apnea is a type of sleep-disordered breathing that is characterized by a failure of the sleeping brain to generate regular, rhythmic bursts of neural activity. The resulting cessation of rhythmic breathing, referred to as apnea, represents a disorder of the respiratory control system responsible for regulating the rate and depth of breathing, i.e. overall pulmonary ventilation. Central sleep apnea should be contrasted with obstructive sleep apnea, where the proximate cause of apnea is obstruction of the pharyngeal airway despite ongoing rhythmic neural outflow to the respiratory muscles. The difference between central sleep apnea and obstructive sleep apnea is clearly established, and the two can co-exist. While central sleep apnea can occur in a number of clinical settings, it is most commonly observed in association with heart failure or cerebral vascular insufficiency. An example of central sleep apnea is Cheyne-Stokes respiration.
The respiratory control system comprises a negative feedback system wherein a central pattern generator creates rhythmic bursts of activity when respiratory chemoreceptors sensing carbon dioxide, oxygen and pH are adequately stimulated (FIG. 1). While this neural output of the brainstem central pattern generator to the respiratory muscles derives from a neural rhythm generated intrinsically by the central pattern generator, the generator becomes silent if the feedback signals, related to arterial PCO2 and PO2, are not sufficiently intense. In other words, the respiratory rhythm is generated by a conditional central pattern generator which requires an adequate input stimulus derived from peripheral chemoreceptors sensing arterial PCO2 and PO2 from central chemoreceptors sensing brain PCO2 /pH. Furthermore, the intensity of neural activity generated by the respiratory central pattern generator depends directly upon the arterial PCO2 inversely on the arterial PO2. Thus, the central and peripheral chemoreflex loops constitute a negative feedback system regulating the arterial PO2 and PCO2, holding them constant within narrow limits (FIG. 1).
This normal regulation of arterial blood gases is accomplished by a stable ventilatory output of the respiratory central pattern generator. By contrast, central sleep apnea represents an instability of the respiratory control system. The instability can arise from one of two mechanisms, namely: (1) intrinsic failure of the respiratory central pattern generator in the face of adequate stimulation by respiratory chemoreceptors; or (2) lack of adequate stimulation of the central pattern generator by respiratory chemoreceptors. The former is referred to as the xe2x80x9cintrinsic instabilityxe2x80x9d and the latter is referred to as the xe2x80x9cchemoreflex instability.xe2x80x9d Theoretically, both mechanisms can co-exist. The common form of central sleep apnea is thought to be caused by the chemoreflex instability mechanism.
The chemoreflex control of breathing might exhibit instability either because the delay of the negative feedback signal is excessively long or because the gain of the system is excessively high. Current evidence indicates that the latter constitutes the principal derangement in central sleep apnea caused by heart failure. Specifically, the overall response of the control system to a change in arterial PCO2 is three-fold higher in heart-failure patients with central sleep apnea than in those having no sleep-disordered breathing. This increased gain probably resides within the central chemoreflex loop; however, high gain of the peripheral chemoreflex loop cannot be excluded. Accordingly, the fundamental mechanism of central sleep apnea is taken to be high loop gain of the control system, which results in feedback instability during sleep.
Central sleep apnea causes repeated arousals and oxyhemoglobin desaturations. Although firm evidence linking central sleep apnea to morbidity and mortality is lacking, a variety of evidence leads to the inference that central sleep apnea may promote cardiac arhythmias, strokes, or myocardial infarctions. The repeated nocturnal arousals are likely to impair daytime cognitive function and quality of life. No treatment has become established as being effective for central sleep apnea. Stimulating drugs such as theophyline may be helpful, and carbonic anhydrase inhibitors may relieve central sleep apnea in normals sleeping at high altitude. Nasal continuous positive airway pressure may directly or indirectly improve ventilatory stability. Increasing inspired fractional concentration (F) of oxygen in the inspired gas generally does not eliminate central sleep apnea, whereas increasing inspired FCO2 (FICO2=0.01-0.03) promptly eliminates central sleep apnea. However, long-term exposure to high FICO2 would appear to be an undesirable long-term therapy.
The present invention is a method for varying the efficiency of pulmonary gas exchange by using a controlled amount of rebreathing during certain periods of the central sleep apnea respiration cycle so as to counteract the effects of the transient excessive ventilation on the level of carbon dioxide and oxygen in the lungs and in the arterial blood. In effect, this strategy is an attempt to stabilize breathing by minimizing oscillations in the feedback variables.
The invention counteracts periodic breathing due to central sleep apnea by decreasing loop gain of the respiratory control system. In one embodiment, the invention dynamically modulates efficiency of pulmonary gas exchange in relation to pulmonary ventilation. When pulmonary ventilation is stable at resting values, the performance of the system is unchanged. However, during a period of hyperpnea, i.e. when ventilation increases transiently to supra-normal levels, the system is made more inefficient, thus decreasing loop gain and stabilizing the system.
Rebreathing can be used to increase the inspired percentage carbon dioxide and reduce the inspired percentage oxygen just before or during the period of overbreathing. In one embodiment, the patient""s ventilation is continuously monitored and analyzed in real time so that the ventilation periodicities of the central sleep apnea breathing can be detected and the inspired carbon dioxide and oxygen concentrations adjusted appropriately by varying the amount of exhaled gas that is reinspired.
In another embodiment of the present invention, a rebreathing apparatus is a part of a nasal continuous positive airway pressure (CPAP) system. The use of continuous positive airway pressure may have a beneficial effect on cardiac function in patients with congestive heart failure. In the future it is likely that patients with congestive heart failure will receive nasal CPAP for treatment of the heart failure. Central sleep apnea may not immediately disappear upon administration of conventional nasal CPAP therapy as central sleep apnea respiration is basically of a non-obstructive origin. However, over a period of about four weeks the degree of heart failure improves; thus, the resulting central sleep apnea respiration may be relieved by the continuous positive airway pressure. This is described in the papers, Naughton, et al., xe2x80x9cEffective Continuous Positive Airway Pressure on Central Sleep Apnea and Nocturnal Percentage Carbon Dioxide in Heart Failure,xe2x80x9d American Journal Respiratory Critical Care Medicine, Vol. 1509, pp 1598-1604, 1994; Naughton, et al., xe2x80x9cTreatment of Congestive Heart Failure and Central Sleep Apnea Respiration during Sleep by Continuous Positive Airway Pressure,xe2x80x9d American Journal of Critical Care Medicine, Vol. 151, pp 92-97, 1995; and, Naughton, et al., xe2x80x9cThe Role of Hyperventilation in the Pathogenesis of Central Sleep Apneas in Patients with Congestive Heart Failure,xe2x80x9d American Review of Respiratory Diseases, Vol. 148, pp 330-338, 1993.
It is desirable to have a prompt elimination of the central sleep apnea respiration because the resulting daytime sleepiness and impaired cognition resulting from repeated arousals impair the patient""s quality of life. Immediately relieving central sleep apnea breathing during the CPAP treatment would have the advantage that the patient would experience a better sleep and would be more rested. This in turn would enhance compliance with the CPAP treatment program. Conventional nasal CPAP provides no immediate relief of central sleep apnea respiration and resulting arousals.
A conventional CPAP system is modified in one embodiment of the present invention to allow a controlled amount of rebreathing during a portion of the central sleep apnea respiration cycle. In this embodiment, a valve is used to control the amount of rebreathing. When the valve is closed, rebreathing occurs and when the valve is open no rebreathing occurs. A computer connected to a flow meter can be used to detect periodicities in the central sleep apnea respiration cycle. The computer can then control the valve to open and close.
Another embodiment of the present invention concerns a passive low-bias-flow device for treating central sleep apnea. This apparatus includes a gas-supply means, such as a blower, and a mask that is fitted on a patient""s face. The gas-supply means is adjusted so that air flow from the gas-supply means is such that for the patient""s normal breathing, the gas flow supplied by the gas-supply means is sufficient to prevent a significant amount of the patient""s exhaled gases from flowing retrograde into a tube between the gas-supply means and the mask. During periods of increased breathing preceding or following central sleep apnea, the preset air flow is such that some of the patient""s exhaled gases flow retrograde into the tube. Some of the exhaled gases flowing retrograde into the tube will be rebreathed by the patient. Thus, during periods of overbreathing associated with central sleep apnea, there will be some rebreathing of gases containing a higher FCO2 and a lower FO2 than room air. Note that conventional CPAP systems are set such that there is no retrograde air flow any time in the sleep cycle.
Yet another embodiment of the present invention is a method for adjusting an apparatus comprising a gas-supply means, a mask and a tube between the mask and the gas-supply means. In this method, the mask is fitted to the patient""s face. The supply of gas from the gas-supply means is set high enough that during the patient""s normal breathing, the gas flow supplied by the gas-supply means is sufficient to prevent a significant amount of the patient""s exhaled gases from flowing retrograde into the tube, but set low enough that during periods of increased breathing increased with central sleep apnea, some of the patient""s exhaled gases flow retrograde into the tube.
Still another embodiment of the present invention concerns an apparatus for treating central sleep apnea wherein the supply of gas from a gas-supply means has a varying gas pressure that changes at different times during the patient""s sleep cycle. In this way, rebreathing can be increased. For example, in one embodiment, the gas pressure from the blower is decreased during periods of increased breathing associated with central sleep apnea so that some of the patient""s exhaled gases flow retrograde between the mask and the blower. This approach is less advantageous because users often find the varying mask pressure to be annoying. Also, varying of the mask pressure can affect the internal dead space in a manner counter to the rebreathing effect.
The general approach is that the blower pressure is set at a minimum level that eliminates all evidence of upper airway obstruction, or at a level deemed appropriate for treating heart failure. The bias flow is then reduced to a level that eliminates central sleep apnea without increasing the external dead space during unstimulated breathing. The bias flow can then be fixed at this level or varied systematically within or between cycles of periodic breathing.